{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T06:12:30Z","timestamp":1778652750322,"version":"3.51.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM135004"],"award-info":[{"award-number":["P20GM135004"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Diagn Ther"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1007\/s40291-026-00840-x","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T04:36:59Z","timestamp":1773117419000},"page":"515-527","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of a Nomogram to Predict Therapeutic Resistance in Metastatic Melanoma Using Longitudinal ctDNA Kinetics"],"prefix":"10.1007","volume":"30","author":[{"given":"Hunter A.","family":"Miller","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalara G.","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael E.","family":"Egger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavitha","family":"Yaddanapudi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maiying","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa B.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2257-0579","authenticated-orcid":false,"given":"Mark W.","family":"Linder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"issue":"1","key":"840_CR1","first-page":"10","volume":"75","author":"RL Siegel","year":"2025","unstructured":"Siegel RL, Kratzer TB, Giaquinto AN, et al. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10\u201345.","journal-title":"CA Cancer J Clin"},{"key":"840_CR2","unstructured":"American Cancer Society. Cancer facts & figures 2025. Atlanta, GA: American Cancer Society."},{"issue":"12","key":"840_CR3","doi-asserted-by":"publisher","first-page":"2722","DOI":"10.1002\/ijc.30407","volume":"39","author":"J Rockberg","year":"2016","unstructured":"Rockberg J, Amelio JM, Taylor A, et al. Epidemiology of cutaneous melanoma in Sweden-stage-specific survival and rate of recurrence. Int J Cancer. 2016;39(12):2722\u20139.","journal-title":"Int J Cancer"},{"issue":"10","key":"840_CR4","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.29681","volume":"4","author":"C Stewart","year":"2021","unstructured":"Stewart C, Smith-Bindman R. Is it time to inform patients of medical imaging risks. JAMA Netw Open. 2021;4(10):e2129681.","journal-title":"JAMA Netw Open"},{"issue":"1","key":"840_CR5","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1001\/jamaophthalmol.2013.564","volume":"131","author":"JC Wen","year":"2013","unstructured":"Wen JC, Sai V, Straatsma BR, et al. Radiation-related cancer risk associated with surveillance imaging for metastasis from choroidal melanoma. JAMA Ophthalmol. 2013;131(1):56\u201361.","journal-title":"JAMA Ophthalmol"},{"issue":"Suppl.1","key":"840_CR6","first-page":"S\u201318S","volume":"48","author":"H Schoder","year":"2007","unstructured":"Schoder H, Gonen M. Screening for cancer with PET and PET\/CT: potential and limitations. J Nucl Med. 2007;48(Suppl.1):S-18S.","journal-title":"J Nucl Med"},{"issue":"1","key":"840_CR7","first-page":"207","volume":"93","author":"MD Howard","year":"2020","unstructured":"Howard MD. Melanoma radiological surveillance: a review of current evidence and clinical challenges. Yale J Biol Med. 2020;93(1):207\u201313.","journal-title":"Yale J Biol Med"},{"issue":"11","key":"840_CR8","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1016\/j.jmoldx.2024.07.001","volume":"26","author":"EM Alexander","year":"2024","unstructured":"Alexander EM, Miller HA, Egger ME, et al.\u00a0The correlation between plasma circulating tumor DNA and radiographic tumor burden. J Mol Diagn. 2024;26(11):952\u201361.","journal-title":"J Mol Diagn"},{"key":"840_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-016-0852-6","volume":"14","author":"M Schreuer","year":"2016","unstructured":"Schreuer M, Meersseman G, Van Den Herrewegen S, et al. Quantitative assessment of BRAF V600 mutant circulating cell-free tumor DNA as a tool for therapeutic monitoring in metastatic melanoma patients treated with BRAF\/MEK inhibitors. J Transl Med. 2016;14:95.","journal-title":"J Transl Med"},{"issue":"5","key":"840_CR10","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1373\/clinchem.2017.281543","volume":"64","author":"V Haselmann","year":"2018","unstructured":"Haselmann V, Gebhardt C, Brechtel I, et al. Liquid profiling of circulating tumor DNA in plasma of melanoma patients for companion diagnostics and monitoring of BRAF inhibitor therapy. Clin Chem. 2018;64(5):830\u201342.","journal-title":"Clin Chem"},{"key":"840_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/PO.18.00229","volume":"3","author":"R V\u00e1raljai","year":"2019","unstructured":"V\u00e1ra\/ljai R, Wistuba-Hamprecht K, Seremet T, et al.\u00a0Application of circulating cell-free tumor DNA profiles for therapeutic monitoring and outcome prediction in genetically heterogeneous metastatic melanoma. JCO Precis Oncol. 2019;3:1\u201310.","journal-title":"JCO Precis Oncol"},{"issue":"224","key":"840_CR12","doi-asserted-by":"publisher","first-page":"224ra24","DOI":"10.1126\/scitranslmed.3007094","volume":"6","author":"C Bettegowda","year":"2014","unstructured":"Bettegowda C, Sausen M, Leary RJ, et al.\u00a0Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24.","journal-title":"Sci Transl Med."},{"issue":"8","key":"840_CR13","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1080\/15384047.2019.1598759","volume":"20","author":"A Kustanovich","year":"2019","unstructured":"Kustanovich A, Schwartz R, Peretz T, et al.\u00a0Life and death of circulating cell-free DNA. Cancer Biol Ther. 2019;20(8):1057\u201367.","journal-title":"Cancer Biol Ther"},{"issue":"5","key":"840_CR14","doi-asserted-by":"publisher","first-page":"357","DOI":"10.2217\/pgs-2018-0174","volume":"20","author":"P Muluhngwi","year":"2019","unstructured":"Muluhngwi P, Valdes R, Fernandez-Botran R, et al.\u00a0Cell-free DNA diagnostics: current and emerging applications in oncology. Pharmacogenomics. 2019;20(5):357\u201380.","journal-title":"Pharmacogenomics"},{"issue":"7","key":"840_CR15","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1080\/10408363.2020.1750558","volume":"57","author":"V Ungerer","year":"2020","unstructured":"Ungerer V, Bronkhorst AJ, Holdenrieder S. Preanalytical variables that affect the outcome of cell-free DNA measurements. Crit Rev Clin Lab Sci. 2020;57(7):484\u2013507.","journal-title":"Crit Rev Clin Lab Sci"},{"issue":"13","key":"840_CR16","doi-asserted-by":"publisher","first-page":"107830","DOI":"10.1016\/j.celrep.2020.107830","volume":"31","author":"R Ariana","year":"2020","unstructured":"Rostami A, Lambie M, Yu CW, et al.\u00a0Senescence, necrosis, and apoptosis govern circulating cell-free DNA release kinetics. Cell Rep. 2020; 31(13):107830.\u00a0https:\/\/doi.org\/10.1016\/j.celrep.2020.107830.","journal-title":"Cell Rep"},{"issue":"30","key":"840_CR17","doi-asserted-by":"publisher","first-page":"48832","DOI":"10.18632\/oncotarget.9453","volume":"7","author":"F Cheng","year":"2016","unstructured":"Cheng F, Su L, Qian C. Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer. Oncotarget. 2016;7(30):48832\u201341.","journal-title":"Oncotarget"},{"issue":"1","key":"840_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75792-1","volume":"10","author":"GT Marczynski","year":"2020","unstructured":"Marczynski GT, Laus AC, Dos Reis MB, et al.\u00a0Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients. Sci Rep. 2020;10(1):18682.","journal-title":"Sci Rep"},{"issue":"2","key":"840_CR19","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.jmoldx.2012.10.002","volume":"15","author":"WO Greaves","year":"2013","unstructured":"Greaves WO, Verma S, Patel KP, et al.\u00a0Frequency and spectrum of BRAF mutations in a retrospective, single-institution study of 1112 cases of melanoma. J Mol Diagn. 2013;15(2):220\u20136.","journal-title":"J Mol Diagn"},{"issue":"48","key":"840_CR20","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000008404","volume":"96","author":"EJ Hannan","year":"2017","unstructured":"Hannan EJ, O\u2019Leary DP, MacNally SP, et al.\u00a0The significance of BRAF V600E mutation status discordance between primary cutaneous melanoma and brain metastases: the implications for BRAF inhibitor therapy. Medicine (Baltimore). 2017;96(48):e8404.","journal-title":"Medicine (Baltimore)"},{"key":"840_CR21","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.ejca.2021.09.019","volume":"158","author":"L Gracie","year":"2021","unstructured":"Gracie L, Pan Y, Atenafu EG, et al.\u00a0Circulating tumour DNA (ctDNA) in metastatic melanoma, a systematic review and meta-analysis. Eur J Cancer. 2021;158:191\u2013207.","journal-title":"Eur J Cancer"},{"key":"840_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2020.103187","volume":"157","author":"S Gandini","year":"2021","unstructured":"Gandini S, Zanna I, De Angelis SP, et al.\u00a0Circulating tumour DNA and melanoma survival: a systematic literature review and meta-analysis. Crit Rev Oncol Hematol. 2021;157:103187.","journal-title":"Crit Rev Oncol Hematol"},{"issue":"5","key":"840_CR23","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/S1470-2045(25)00139-1","volume":"26","author":"MM Syeda","year":"2025","unstructured":"Syeda MM, Long GV, Garrett J, et al.\u00a0Clinical validation of droplet digital PCR assays in detecting BRAF(V600)-mutant circulating tumour DNA as a prognostic biomarker in patients with resected stage III melanoma receiving adjuvant therapy (COMBI-AD): a biomarker analysis from a double-blind, randomised phase 3 trial. Lancet Oncol. 2025;26(5):641\u201353.","journal-title":"Lancet Oncol"},{"issue":"18","key":"840_CR24","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1056\/NEJMoa2404139","volume":"391","author":"GV Long","year":"2024","unstructured":"Long GV, Santinami M, Kirkwood JM, et al. Final results for adjuvant dabrafenib plus trametinib in stage III melanoma. N Engl J Med. 2024;391(18):1709\u201320.","journal-title":"N Engl J Med"},{"issue":"3","key":"840_CR25","doi-asserted-by":"publisher","first-page":"e001504","DOI":"10.1136\/jitc-2020-001504","volume":"9","author":"B Ricciuti","year":"2021","unstructured":"Ricciuti B, Jones G, Severgnini M, et al.\u00a0Early plasma circulating tumor DNA (ctDNA) changes predict response to first-line pembrolizumab-based therapy in non-small cell lung cancer (NSCLC). J Immunother Cancer. 2021;9(3):e001504.\u00a0https:\/\/doi.org\/10.1136\/jitc-2020-001504.","journal-title":"J Immunother Cancer"},{"issue":"15","key":"840_CR26","doi-asserted-by":"publisher","first-page":"3913","DOI":"10.3390\/cancers13153913","volume":"13","author":"SH Tolmeijer","year":"2021","unstructured":"Tolmeijer SH, Koornstra RHT, de Groot JWB, et al.\u00a0Plasma BRAF mutation detection for the diagnostic and monitoring trajectory of patients with LDH-high stage IV melanoma. Cancers. 2021;13(15):3913.","journal-title":"Cancers"},{"issue":"3","key":"840_CR27","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1158\/0008-5472.CAN-21-1718","volume":"82","author":"J-C Stadler","year":"2022","unstructured":"Stadler J-C, Belloum Y, Deitert B, et al.\u00a0Current and future clinical applications of ctDNA in immuno-oncology. Cancer Res. 2022;82(3):349\u201358.","journal-title":"Cancer Res"},{"key":"840_CR28","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1200\/PO.19.00174","volume":"4","author":"J Braune","year":"2020","unstructured":"Braune J, Keller L, Schiller F, et al.\u00a0Circulating tumor DNA allows early treatment monitoring in BRAF- and NRAS-mutant malignant melanoma. JCO Precis Oncol. 2020;4:20\u201331.","journal-title":"JCO Precis Oncol"},{"issue":"12","key":"840_CR29","doi-asserted-by":"publisher","first-page":"3793","DOI":"10.3390\/cancers12123793","volume":"12","author":"G Marsavela","year":"2020","unstructured":"Marsavela G, Johansson PA, Pereira MR, et al.\u00a0The prognostic impact of circulating tumour DNA in melanoma patients treated with systemic therapies: beyond BRAF mutant detection. Cancers (Basel). 2020;12(12):3793.\u00a0https:\/\/doi.org\/10.3390\/cancers12123793.","journal-title":"Cancers (Basel)"},{"key":"840_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2024.101883","volume":"42","author":"ME Egger","year":"2024","unstructured":"Egger ME, Alexander E, Van Meter T, et al.\u00a0Corresponding ctDNA and tumor burden dynamics in metastatic melanoma patients on systemic treatment. Transl Oncol. 2024;42:101883.","journal-title":"Transl Oncol"},{"issue":"3","key":"840_CR31","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s40291-021-00528-4","volume":"25","author":"MW Linder","year":"2021","unstructured":"Linder MW, Egger ME, Van Meter T, et al.\u00a0Longitudinal relationship between idylla plasma ctBRAF V600 mutation detection and tumor burden in patients with metastatic melanoma. Mol Diagn Ther. 2021;25(3):361\u201371.","journal-title":"Mol Diagn Ther"},{"issue":"6","key":"840_CR32","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1177\/0272989X06295361","volume":"26","author":"AJ Vickers","year":"2006","unstructured":"Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Mak. 2006;26(6):565\u201374.","journal-title":"Med Decis Mak"},{"issue":"39","key":"840_CR33","doi-asserted-by":"publisher","first-page":"42008","DOI":"10.18632\/oncotarget.5788","volume":"6","author":"ES Gray","year":"2015","unstructured":"Gray ES, Rizos H, Reid AL, et al\u00a0Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma. Oncotarget. 2015;6(39):42008\u201318.","journal-title":"Oncotarget"},{"issue":"1","key":"840_CR34","volume":"18","author":"Y Pan","year":"2025","unstructured":"Pan Y, Wang H, Wang H. Diagnostic value of CT on lymph node metastasis in patients with penile cancer and analysis of related influencing factors. J Radiat Res Appl Sci. 2025;18(1):101288.","journal-title":"J Radiat Res Appl Sci"},{"issue":"1","key":"840_CR35","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-021-00306-8","volume":"9","author":"CC Ko","year":"2021","unstructured":"Ko CC, Yeh LR, Kuo YT, et al.\u00a0Imaging biomarkers for evaluating tumor response: RECIST and beyond. Biomark Res. 2021;9(1):52.","journal-title":"Biomark Res"},{"key":"840_CR36","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.800547","volume":"11","author":"L Fournier","year":"2021","unstructured":"Fournier L, de Geus-Oei LF, Regge D, et al.\u00a0Twenty years on: RECIST as a biomarker of response in solid tumours: an EORTC Imaging Group-ESOI joint paper. Front Oncol. 2021;11:800547.","journal-title":"Front Oncol"},{"issue":"6","key":"840_CR37","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1007\/s00330-009-1685-y","volume":"20","author":"EL van Persijn van Meerten","year":"2010","unstructured":"van Persijn van Meerten EL, Gelderblom H, Bloem JL. RECIST revised: implications for the radiologist: a review article on the modified RECIST guideline. Eur Radiol. 2010;20(6):1456\u201367.","journal-title":"Eur Radiol"},{"issue":"5","key":"840_CR38","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1093\/annonc\/mdx026","volume":"28","author":"JH Lee","year":"2017","unstructured":"Lee JH, Long GV, Boyd S, et al.\u00a0Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma. Ann Oncol. 2017;28(5):1130\u20136.","journal-title":"Ann Oncol"}],"container-title":["Molecular Diagnosis & Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40291-026-00840-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40291-026-00840-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40291-026-00840-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:46:25Z","timestamp":1778651185000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40291-026-00840-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["840"],"URL":"https:\/\/doi.org\/10.1007\/s40291-026-00840-x","relation":{},"ISSN":["1177-1062","1179-2000"],"issn-type":[{"value":"1177-1062","type":"print"},{"value":"1179-2000","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]},"assertion":[{"value":"27 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors acknowledge funding in the form of reagents and supplies from BioRaD. Funding for these studies was also provided through the Department of Pathology and Laboratory of Medicine, National Institutes of Health P20GM135004 pilot project program as well as access to gift funding through the UofL Health Brown Cancer Center.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Hunter A. Miller, Annalara Fischer, Michael E. Egger, Kavitha Yaddanapudi, Maiying Kong, and Melissa B. Hall have no conflicts of interest that are directly relevant to the content of this article. Mark W. Linder is an Editorial Board member of\n                      Molecular Diagnosis & Therapy\n                      . Mark W. Linder was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest\/competing interests"}},{"value":"Patient plasma samples used for this study were selected from patients with a diagnosis of cutaneous melanoma with longitudinal samples collected by the UofL Health Brown Cancer Center Multi-Disciplinary Melanoma Clinic biorepository at the University of Louisville from 2018 through 2022 under an ongoing Institutional Review Board-approved protocol (IRB #08.0388). This study was determined to be exempt from Institutional Review Board review (reference number #673708).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"HAM: data curation (lead); formal analysis (lead); methodology (lead); software (lead); visualization (lead); writing (original draft) [lead]; writing (review and editing) [lead]. AF: investigation (supportive); data curation (supportive); writing (review and editing) [supportive]. MEE: conceptualization (supportive); investigation (supportive); writing (review and editing) [supportive]. KY: conceptualization (supportive); writing (review and editing) [supportive]. MK: validation (lead); writing (review and editing) [supportive]. MH: resources (supportive); data curation (supportive); writing (review and editing) [supportive]. Mark W. Linder: conceptualization (lead); funding acquisition (lead); investigation (lead); project administration (lead); resources (lead); supervision (lead); writing (original draft) [supportive]; writing (review and editing) [supportive]. All authors have read and approved the final version of the article.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 contributions"}}]}}